Efficacy of HOFA Versus Hydrocolloid Dressings in the Prevention of PUs in Critically Ill Prone Patients

INTRODUCTION Multiple studies have shown that Prone position (PP) alters the mechanics and physiology of gas exchange to result in improved oxygenation, especially if used early (first 48 hours) in appropriate patients. However, it´s carries complications, some associated with prolonged decubitus, as the pressure ulcers (PUs) on the pelvis, thorax, knees and face. Dressings and topical agents intended for the prevention of skin injuries are widely used. However, it is not clear which ones are most effective in preventing PUs in the prone patient. On the other hand, it is important to take into account the great impact that PUs have on the quality of life of patients, the increase in hospitalization times and the high costs involved, so it´s important to focus nursing care on their prevention. Given the current variability in the interchangeable use of hydrocolloid dressings (HCD) and hyperoxygenated fatty acids (HOFA) in the prevention of PUs in patients admitted to the ICU, and given that there is insufficient scientific evidence to support the use of one method of prevention versus the other when the critical patient is placed on PP, it was considered necessary to carry out a clinical trial.

HYPOTHESIS: PUs in Intensive Care Units have been shown to be multicausal, so that there is a great variability in the incidence of these diseases. For that reason, when establishing the comparison between HOFA methods and hydrocolloid dressings, it is expected to find a lower incidence with the use of HOFA.

METHODOLOGY Design: A randomized controlled clinical trial with two comparison groups will be performed (Group A: hyperoxygenated fatty acids;Group B: hydrocolloid dressing). Study period: prior to initiation of the multicenter phase, a 6-month pilot study (June-December 2021) was conducted at the coordinating center to assess the methodological and operational feasibility of the protocol, as well as to standardize recruitment, intervention, follow-up, and data collection procedures. During this period, a total of 26 patients were enrolled. From January 2022 to January 2026, an additional 200 subjects had been recruited. Subjects and study setting: Patients admitted to Intensive Care Units in hospitals participating in the project who are prescribed DP maneuver with signed or authorized consent from their referring family member. This is a multicenter study involving 7 ICUs from 7 hospitals in the National Health System: Puerta de Hierro Majadahonda University Hospital (leading center ECA), Torrejón University Hospital, La Princesa University Hospital, San Carlos Clinical University Hospital, La Paz University Hospital, Central University Hospital of Asturias, University Hospital of Navarra.

Randomization: All patients admitted to the ICU who meet the inclusion criteria will be randomized into two groups, according to a randomization list prepared by Care Research Unit from MPHUH before starting the study, using a pseudo-random number generator program (Epidat program version 3.1). The distribution will be revealed by means of opaque, numbered, sealed and correlated envelopes, at the time the study subject is recruited.

Before performing the PP maneuver, regardless of the assigned group, the hygiene and hydration care established by the Unit's protocols will be carried out. Subsequently, the care assigned to each group will be carried out. Once the group is assigned (HOFA or HCD), an infographic will be placed in the box with a summary of care to ensure continuity of care. In the event that more prone sessions are required, the same care assigned at the beginning will be maintained in the following sessions.

Blinding: In this type of study, the aim is to guarantee internal validity by minimizing possible biases, which is why it is important to guarantee the randomization process and the measurement of variables with objective criteria. This type of clinical trial does not allow masking the person who performs the intervention, nor the person who measures the main outcome variable, since given the type of patient and the specific care required, it is not possible for a professional outside the patient's care to carry out the assessment of the patient. Blinded analysis of the patients will be guaranteed.

Study termination criteria: Clinical deterioration of the patient, which either causes PP to be halted before the stipulated time or does not allow data-collection to be completed after the end of the PP session due to clinical exacerbation; patient death which has prevented completion of the PP-SP session and collection of data post-pronation; revocation of signed consent by the family or patient; or termination of clinical indication of PP before the data-collection cycle has been completed.

Recruitment and conduct of the study: Patients admitted to Intensive Care Units in the hospitals participating in the project who are prescribed DP maneuvers, who do not have prior pressure injuries related to previous DP, with signed consent or authorized by their referring family member.

PP treatment is carried out in critically ill or very critically ill patients, previously sedated in most cases, so that, in general, it will not be possible to obtain the patient's prior consent. In addition, given the urgency in some cases of this clinical decision and the prohibition of visits due to the current COVID-19 pandemic, it will not be possible in many cases to obtain prior written informed consent (IC) from the family. Whenever possible, an information sheet and informed consent will be provided to the family in person. If it is not possible to obtain the written IC, the ICU staff will contact a member of the research team or the collaborating medical team, who will be in charge of informing and obtaining, as soon as possible, the IC by means of a telephone call to the reference family member. If the family refuses to participate, the patient will be removed from the study for that reason and the pre-established data cannot be collected. In this case, the subject would be treated as lost to follow-up for cause.

Study variables: The main outcome variable will be the occurrence of PU, location, extent and severity. In addition, other patient profile variables, clinical variables, treatment and care, PP-related complications, adverse events related to the use of HOFA or HCD will be analyzed. All the data to be collected at the different moments of assessment are specified in the field notebook.

Data collection: A register will be kept in which all patient data will be included and assigned a code (the same code that corresponds to the randomization envelope: 001, 002, 003, etc.). A Data Collection Sheet will be prepared for each patient. Part of the information will be collected in situ at the time of the PP maneuver. The rest of the data will be collected from the electronic medical record in the clinical programs. All this is detailed in the Field Notebook. Data will be collected at the time of patient inclusion in the study, before and after performing the prone position maneuver, and 24 hours after the maneuver, with the corresponding follow-up in the event of complications. This data collection will be repeated each time the patient requires PP during their stay in the ICU. At the time of inclusion in the study, a sealed envelope containing the infographic corresponding to the assigned group, the field notebook and the informed consent form will be taken. In this way, if the research team is not present at the time, the personnel in charge of performing the maneuver will be able to collect the initial data in real time. The rest of the variables will be collected, always in coded form, by the research team. An initial sheet with general data relating to the patient at the time of inclusion in the study and an activity sheet with data relating to each prone maneuver will be collected. As many activity sheets will be included as prognoses are performed on the patient.

Statistical analysis: Two online forms have been designed to securely record data online, one for collecting general patient data at the time of recruitment (Initial Form) and another for gathering data related to the Case Report Form necessary each time the patient is mobilized (DS/DP/DS) with all the variables. These online forms allow each ICU to securely and in real-time enter the collected data from each of the patients recruited in the study, with the corresponding coding. The data is collected by the clinical research team in each participating ICU, who will ensure the quality of the data and the proper completion of the CRD. Analyses will be performed per assigned protocol. Means, medians, standard deviations and ranges of quantitative variables and percentages of qualitative variables will be presented in tabular form. Different analyses will be carried out to compare the outcome variables in the two groups, using the appropriate statistical tests (parametric and non-parametric), depending on the variables and the characteristics of the distribution. Possible losses to follow-up and the reasons will be recorded. Possible adverse effects will be recorded. Mean differences for qualitative measures and relative risks, absolute and relative risk reductions and number needed to treat qualitative variables will be presented. For all outcome variables, 95% confidence intervals will be presented. The level of statistical significance is set at a level below 0.05. Data analysis will be carried out using SPSS and/or STATA statistical software.

WORK PLAN AND SCHEDULE: The present study was prepared following the development of the internal protocol "Procedure: Prone Maneuver HUPHM-UCI-PR-089-01", approved by the MPHUH Departments of Quality and Nursing Management in December 2020.

PHASE I. PREPARATORY. Preparation of material and training.

• Development of the internal protocol "Prone Position Maneuver" (PI and Co-PI) approved by Quality and Nursing Management (December 2020).
• Training of ICU staff from the reference hospital (Hospital Puerta de Hierro Majadahonda) (February-June 2021) by the project coordinators (PI and Co-PI).
• Training of the centers included in the later phase through online sessions to unify criteria and protocols (June 2021-March 2023) by the project coordinators (PI and Co-PI).

PHASE II. INTERVENTION. Implementation of the intervention.

• Multicenter conversations and coordination (February 2021- present)
• 6-month pilot study (June-December 2021) in the ICU of the reference hospital (Hospital Puerta de Hierro Majadahonda) with 26 patients recruited by clinical researchers.
• Start of data collection from 3 hospitals in the Community of Madrid by clinical researchers: Hospital Universitario Torrejón (November 2021), Hospital Universitario La Princesa (May 2022), Hospital Universitario Clínico San Carlos (October 2022) - Incorporation of 3 new hospitals at the national level following the approval of their respective CEIm (2023): Hospital Universitario La Paz, Hospital Universitario Central de Asturias, Hospital Universitario de Navarra.

PHASE III. MONITORING. Data collection.

• Creation of a computerized database on a digital platform in process by the Principal Investigator, with advice from the Training and Research Department (2022).
• Inclusion in the digitized database of the data collected at the promoting center to perform a preliminary analysis of the same, considering the possible adjustment of the sample size by the Department of Research and Biostatistics (Analysis in progress).
• Inclusion in the digitized database of the data collected in the collaborating centers (September 2024-Currently) for subsequent analysis.
• The study will remain active until the sample size is completed, continuing data collection by the clinical team, under the supervision of the project coordinators.